The ability of a malignant tumor to utilize preferentially metabolic products from normal tissues in the host organism is of obvious importance for the normal proliferation of the malignancy as well as for controlling this growth by therapeutic manipulation of the metabolic difference. Past studies in our laboratory revealed an enzyme difference in normal and malignant hepatocytes with respect to succinyl-CoA: acetoacetate CoA transferase. The presence of this enzyme in rat (and mouse) hepatomas allows for the utilization of ketone bodies (presumably produced by the liver which essentially lacks CoA transferase). The proposal outlines additional studies relating to several aspects of ketone body metabolism in hepatoma-bearing Buffalo rats. These include: 1) determining ketone body levels in blood, liver and tumors of normal and tumor-bearing rats; 2) surveying rat hepatomas for another enzyme, acetoacetyl-CoA synthase, that may also be involved in ketone body utilization; 3) continuing to survey for CoA transferase inhibitors (or, in general, inhibitors of ketone body consumption) using purified enzymes from normal and malignant tissues; 4) ascertaining the effects of ketone bodies and selected enzyme inhibitors on the growth characteristics of cultured adult liver and hepatoma cells; and 5) determining the disposition of radioisotopically-labeled Beta-hydroxybutyrate and acetoacetate in tumors using tissue slice and cultured cell techniques. The results of these studies will better define the role of ketone body metabolism in hepatoma-bearing organisms, possibly provide a new and simple diagnostic technique (namely, measurement of blood ketone body levels) for detecting the presence of a liver malignancy, and possibly afford novel chemotherapeutic agents for limiting the growth of malignant hepatomas. BIBLIOGRAPHIC REFERENCES: A. Fenselau and K. Wallis, "3-Oxo Acid Coenzyme A Transferase in Normal and Diabetic Rat Muscle," Biochem. J., 158, 509-512 (1976). A. Fenselau, K. Wallis and H.P. Morris, "Subcellular Localization of Acetoacetate Coenzyme A Transferase in Rat Hepatomas," Cancer Res., 36, 4429-4433 (1976).